To collect information about the wide spectrum of mitochondrial diseases, NAMDC has designed and implemented a comprehensive mitochondrial disease Clinical Registry, which gathers baseline clinical, biochemical, and molecular genetic data as well as tracks the natural histories of the patients through the NAMDC Clinical Longitudinal study. The overall missions of the NAMDC Clinical Registry are to: better understand the spectrum and overlap of phenotypes for specific mitochondrial diseases; enable genotype/phenotype correlations; facilitate enrollment into clinical studies under NAMDC arid other entities; and characterize the natural histories of mitochondrial diseases. More than 425 patients have been enrolled across 13 NAMDC sites in collaboration with the United Mitochondrial Disease Foundation (UMDF). We have also created NAMDC Research Diagnostic Criteria for mitochondrial diseases with strict benchmarks for definite, probable, possible, or unlikely levels of diagnoses. Samples of blood, skin, and other tissues are being deposited into the NAMDC Biorepository housed at the Mayo Clinic under the direction of Dr. Devin Oglesbee. The NAMDC Clinical Registry, Research Diagnostic Criteria, and Biorepository are three pillars that form a strong foundation for multi-center collaborative mitochondrial disease research. From this firm base, productive patient-oriented projects have already sprouted; natural history studies on mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), Alpers disease, and Pearson syndrome have been initiated by NAMDC site investigators. This project seeks: to expand the NAMDC Clinical Registry and Biorepository; to continue to on-going natural history studies including the Clinical Longitudinal study, to apply and refine the NAMDC Research Diagnostic Criteria; to support the MNGIE AHSCT Safety Study (MASS, Project 2); to strengthen links to mitochondrial disease sequence data resource (MSeqDR) consortium; and to support new research projects including the Natural History and Advanced Genetic Studies of PDC Deficiency (Project 3); and the studies of nutritional supplements for mitochondrial diseases.